Zoledronic Acid (ZOL 446) is a bisphosphonate. Zoledronic Acid (ZOL 446) is used to prevent skeletal fractures in patients with cancers such as multiple myeloma and prostate cancer. It can also be used to treat hypercalcemia of malignancy and can be helpful for treating pain from bone metastases. An annual dose of Zoledronate may also prevent recurring fractures in patients with a previous hip fracture. Zoledronic Acid (ZOL 446) is a single 5 mg infusion for the treatment of Paget's disease of bone. In 2007, the FDA also approved Reclast for the treatment of postmenopausal osteoporosis.

Calcitonin is a peptide hormone that lowers blood calcium level and inhibits bone resorption. It belongs to the calcitonin family of peptides, which also includes amylin , calcitonin gene-related peptide , and adrenomedullin. The binding of salmon calcitonin to the human calcitonin receptor (CTR) is not modulated by receptor activity-modifying proteins (RAMPs), which influence affinity of human calcitonin to CTR. Salmon calcitonin binds to human CTR2 with IC50 values of 0.933, 0.224, 0.134, and 0.317 nM alone and with RAMP1, 2, or 3, respectively. It induces cAMP accumulation in COS-7 cells transfected with CTR2 (EC50 = 0.166 nM). Salmon calcitonin inhibits bone resorption by osteoclasts in a pit formation assay using rat bone slices (ID50 = 0.003 pg/mL) and lowers calcium level in vivo in a bioassay of hypocalcemia in rats (ED15 = 33.9 mg/kg). Formulations containing salmon calcitonin have been used to treat hypercalcemia, bone destruction by osteoporosis, and Paget's disease.

Sodium etidronate (Didronel) is a synthetic therapeutic diphosphonate analog of endogenous pyrophosphate. As a member of the family of drugs known as bisphosphonates, Sodium etidronate differs from endogenous pyrophosphate in its resistance to enzymatic hydrolysis. This agent adsorbs to hydroxyapatite cells and reduces the number of osteoclasts, thereby inhibiting abnormal bone resorption. Etidronate may also directly stimulate bone formation by osteoblasts.

Osteocalcin (1-49) is a non-collagenous peptide that is secreted by osteoblasts and odontoblasts and comprises 1-2% of the total protein in bone. Secretion of osteocalcin (1-49) is stimulated by 1,25-dihydroxy vitamin D and plasma levels increase in diseases that induce dysregulated bone turnover such as osteoporosis, Paget's disease, and primary hyperparathyroidism. Osteocalcin (1-49) is positively correlated with insulin sensitivity and negatively correlated with high blood glucose levels in women. In vitro, osteocalcin induces chemotaxis of MDA-MB-231 breast cancer cells, human peripheral blood monocytes, and rat osteosarcoma cells with osteoblast-like characteristics. It is also expressed by vascular smooth muscle cells (VSMCs) displaying an osteoblast-like phenotype and has been positively associated with calcification of aortic tissue and heart valves in humans.

Etidronic acid (HEDP) is a diphosphonate which affects calcium metabolism. It inhibits ectopic calcification and slows down bone resorption and bone turnover.